Glycosylphosphatidylinositol membrane anchor

J. O. Previato, C. Jones, L. P. B. Gonsalves, R. Wait, L. R. Travassos, A. J. Parodi, and L. Vlendonga-Previato, Structural characterization of the major glycosylphosphatidylinositol membrane-anchored glycoprotein from epimastigote forms of Trypanosoma cruzi Y-strain, J. Biol. Chem., 270 (1995) 7241-7250. 

M. L. Guther, M. L. de Almeida, N. Yoshida, and M. A. J. Ferguson, Structural studies on the glycosylphosphatidylinositol membrane anchor of Trypanosoma cruzi lG7-antigen. The structure of the glycan core,./. Biol. Chem., 267 (1992) 6820-6828. 

G. Sipos, A. Puoti, and A. Conzelmann, Glycosylphosphatidylinositol membrane anchors in Saccharomyces cerevisiae absence of ceramides from complete precursor glycolipids, EMBO... 

Previato JO, Jones C, Xavier MT et al. Structural characterization of the major glycosylphosphatidylinositol membrane-anchored glycoprotein from epimastigote forms of Trypanosoma cruzi Y-strain. J Biol Chem 1995 270 7241-7250. 

Glycosylphosphatidylinositol membrane anchor. Glycosylphospho-tidylinositol (GPI) groups function to anchor a wide variety of proteins to exterior surface of the eukaryotic plasma membrane as a transmembrane polypeptide domain. The core GPI is synthesized on the lumenal side of ER (Tartakoff and Singh, 1992), as shown in... 

C. Fankhauser, S. W. Homans, J. E. Thomas-Oates, M. J. McConville, C. Desponds, A. Conzelmann M. A. Ferguson. Structures of glycosylphosphatidylinositol membrane anchors from Saccharomyces cerevisiae. J Biol Chem, 1993, 268, 26365-26374. 

S. W. Homans, C. J. Edge, M. A. Ferguson, R. A. Dwek T. W. Rademacher. Solution structure of the glycosylphosphatidylinositol membrane anchor glycan of Trypanosoma brucei variant surface glycoprotein. Biochemistry, 1989, 28, 2881-2887. 

M. A, Ferguson. Site of palmitoylation of a phospholipase C-resistant glycosylphosphatidylinositol membrane anchor. Biochem J, 1992, 284, 297-300. 

D. K. Sharma, T. K. Smith, A. Crossman, J. S. Brimacombe M. A. Ferguson. Substrate specificity of the N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase of glycosylphosphatidylinositol membrane anchor biosynthesis in African trypanosomes and human cells. Biochem J, 1997, 328, 171-177. 

M. C. Field, A. K. Menon G. A. Cross. Developmental variation of glycosylphosphatidylinositol membrane anchors in Trypanosoma brucei. Identification of a candidate biosynthetic precursor of the glycosylphosphatidylinositol anchor of the major procyclic stage surface glycoprotein. J Biol Chem, 1991, 266, 8392-8400. 

G. Sipos, F. Reggiori, C. Vionnet A. Conzelmann. Alternative lipid remodelling pathways for glycosylphosphatidylinositol membrane anchors in Saccharomyces cerevisiae. EMBO J, 1997, 16, 3494-3505. 

Much of the plasma membrane cholesterol is removed by incubating cells with P-methylcyclodextrin for several hours. Cells remain viable after this treatment but the raft fraction is reduced and it is inferred that the depleted proteins are normally associated with cholesterol-dependent lipid rafts. Some, but not all, glycosylphosphatidylinositol (GPI)-anchored proteins are recovered in the fractions defined by this procedure. 

A bacterial phosphatidylinositol specific phospholipase C (PI-PLC) had been available for many years before it was demonstrated to strip a number of membrane-bound proteins from eukaryotic cell surfaces [1], Such proteins are anchored by a PI moiety in which the 6 position of inositol is glycosidically linked to glucosamine, which in turn is bonded to a polymannan backbone (Fig. 3-10). The polysaccharide chain is joined to the carboxyl terminal of the anchored protein via amide linkage to ethanolamine phosphate. The presence of a free NH2 group in the glucosamine residue makes the structure labile to nitrous acid. Bacterial PI-PLC hydrolyzes the bond between DAG and phosphati-dylinositols, releasing the water-soluble protein polysac charide-inositol phosphate moiety. These proteins are tethered by glycosylphosphatidylinositol (GPI) anchors. 

Furthermore, according to Howell and Crine (1996), type IV represents multimers of subunits, type V represents proteins that are anchored to the membrane by a covalently linked lipid moiety only, and type VI represents those anchored both by a transmembrane domain and the glycosylphosphatidylinositol (GPI) anchor (see Section III,C,3). 

The last class of three major membrane anchors is caused by the modification by a glycophospholipid, glycosylphosphatidylinositol (GPI) (Udenfriend and Kodukula, 1995a Takeda and Kinoshita, 1995). They are observed in many eukaryotes, especially in protozoa and yeasts. Unlike other classes, the GPI-anchored proteins are exposed at the (extracytoplasmic) surface of the plasma membrane. Thus, we can predict the localization at the plasma membrane from the presence of a GPI anchor, although some of them are further incorporated into the cell wall in S. cerevisiae (as described in Section III,K,1). 

Molecular targets have been elucidated for Dm-AMPl and Rs-AFP2. Dm-AMPl was found to bind plasma membranes from Neurospora crassa and Saccharomyces cerevisiae in a saturable manner and it competed with closely related defensins for binding. Mutational studies with S. cerevisiae identified lipid raffs containing sphingolipids as a molecular target " while glycosylphosphatidylinositol (GPI)-anchored proteins could be... 

Glycosylphosphatidylinositols (GPI anchors 14) are a class of naturally occu-ring glycophospholipids that do not only bind the C-termini of membrane protein but also mediate signal transduction. Several papers have been devoted to their syntheses. Most of them have a structure related to 14 (with various side-chains that are species-specific) but some yeast GPI have been reported to... 

Scheme 13 Structure of the Natural Protein Membrane Anchor Glycosylphosphatidylinositol...

Figure 8-13 Structure of glycosylphosphatidylinositol (also called phospha-tidylinositol-glycan) membrane anchors. The core structure is shown in black. The green parts are found in the Thy-1 protein and / or in other anchors.

Phosphatidylinositol (PI), a major component of membrane lipids, is formed by displacement of CMP from CMD-dialylglycerol by n/i/o-inositol.186 It is also converted into a variety of less abundant phosphory-lated derivatives that engage in signaling activities (see Fig. 11-9). In addition, PI is a component of the glycosylphosphatidylinositol (GPI) membrane anchors for suface proteins (Fig. 8-13). Free GPI anchors, lacking bound proteins, are also present in membranes. 

Receptors anchored to the plasma membrane by lipids Glycosylphosphatidylinositol (GPI)-anchored proteins and glycolipids... 

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